Abstract
Human aging is associated with a decrease in tissue functions combined with a decline in stem cells frequency and activity followed by a loss of regenerative capacity. The molecular mechanisms behind this senescence remain largely obscure, precluding targeted approaches to counteract aging. Focusing on mesenchymal stromal/stem cells (MSC) as known adult progenitors, we identified a specific switch in miRNA expression during aging, revealing a miR-196a upregulation which was inversely correlated with MSC proliferation through HOXB7 targeting. A forced HOXB7 expression was associated with an improved cell growth, a reduction of senescence, and an improved osteogenesis linked to a dramatic increase of autocrine basic fibroblast growth factor secretion. These findings, along with the progressive decrease of HOXB7 levels observed during skeletal aging in mice, indicate HOXB7 as a master factor driving progenitors behavior lifetime, providing a better understanding of bone senescence and leading to an optimization of MSC performance. Stem Cells 2015;33:939-950
Original language | English |
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Pages (from-to) | 939-950 |
Number of pages | 12 |
Journal | Stem Cells |
Volume | 33 |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar 1 2015 |
Keywords
- Aging
- Bone
- Bone marrow stromal cells
- Homeobox genes
ASJC Scopus subject areas
- Cell Biology
- Developmental Biology
- Molecular Medicine
- Medicine(all)